David H. Hubel and Torsten N. Wiesel’s Research on Optical Development in Kittens

By Dina Ziganshina
Published: 2017-10-11
Keywords:

David H. Hubel and Torsten N. Wiesel’s Research on Optical Development in Kittens

During 1964, David Hubel and Torsten Wiesel studied the short and
long term effects of depriving kittens of vision in one eye. In their
experiments, Wiesel and Hubel used kittens as models for human children.
Hubel and Wiesel researched whether the impairment of vision in one eye
could be repaired or not and whether such impairments would impact
vision later on in life. The researchers sewed one eye of a kitten shut
for varying periods of time. They found that when vision impairments
occurred to the kittens right after birth, their vision was
significantly affected later on in life, as the cells that were
responsible for processing visual information redistributed to favor the
unimpaired eye. Hubel and Wiesel worked together for over twenty years
and received the 1981 Nobel Prize for Physiology or Medicine for their
research on the critical period for mammalian visual system development.
Hubel and Wiesel’s experiments with kittens showed that there is a
critical period during which the visual system develops in mammals, and
it also showed that any impairment of that system during that time will
affect the lifelong vision of a mammal.

In 1959, David Hubel
and Torsten Wiesel met in John Hopkins Medical School in Baltimore,
Maryland, where they worked in Stephen Kuffler’s neuroscience lab. That
same year Kuffler and the staff of his laboratory moved to Harvard
Medical School in Boston, Massachusetts. While working in Kuffler’s new
lab at Harvard, Hubel and Wiesel conducted a series of experiments on
cats and kittens as models for humans, and in the 1970s they repeated
the experiments on primates. Their collaboration lasted for over twenty
years, during which time Hubel and Wiesel elucidated details about the
development of the visual system.

During the 1960s,
scientists did not fully understand the development of the visual
system, although Kuffler and his laboratory staff studied it closely.
Researchers had yet to discover the connection between the retina, a
layer of light sensitive cells on the backside of the eye, and the
visual cortex of the brain. As of 2017, scientists know that the visual
system consists of the eye, the optic nerve, the lateral geniculate
body, and the visual cortex of the brain. The retina of the eye has rods
and cones that receive visual stimuli that include colors and the forms
of objects. That information is sent to the brain through the optic
nerve. In the brain, the optic nerves from each eye cross at the optic
chiasm, which is a cross formed by the optic nerves on the bottom of the
brain. The right optic nerve becomes the left optic tract and the left
optic nerve becomes the right optic tract. The optic tracts further
carry the visual information into the brain and end at lateral
geniculate body in the thalamus, which is a small part of the brain that
serves as a relay for sensory information from the eyes to the brain.
The lateral geniculate body has geniculate cells that are at a midpoint
between the eye and the visual cortex. After that, the information is
transferred to the visual cortex, which is the largest area of the brain
that is responsible for interpreting visual information and is located
on the outer backside of the brain called the occipital lobe. The visual
cortex has cortical cells that are responsible for processing and
interpreting visual information.

In 1964 at the time the article
was published, surgeons operated on individuals with congenital
cataracts, a disorder in which the lens of the eye is clouded upon
birth, later in those individuals’ lives rather than at birth. Those
individuals required intensive treatment after surgery, as there was
still impairment to vision in the affected eye. Hubel and Wiesel
questioned why their vision remained impaired. Hubel and Wiesel
hypothesized that there was a time period during which the visual nerve
cells develop and that if the retina did not receive any visual
information at that time, the cells of the visual cortex redistribute
their response in favor of the working eye. By 1964, Hubel and Wiesel
performed a set of experiments to test their hypothesis. Other
researchers had studied the behavior and vision of animals after they
were raised in the dark, but Hubel and Wiesel were the first to study
animal behavior after physically suturing one of the eyes, thus further
reducing the visual input to the retina.

For the purpose of
the experiment, Hubel and Wiesel used newborn kittens and sutured one of
their eyes shut for the first three months of their lives. The sutured
eye did not get any visual information and received 10,000 to 100,000
times less light than the normal eye. That meant that there was no
visual information for the retina of the sutured eye to record and thus
the visual cortex could not receive any input from that eye. Hubel and
Wiesel used four kittens for the experiment.

After three
months, Hubel and Wiesel opened the sutured eyes, and recorded the
changes. They found a noticeable difference in cortical cell response.
The researchers recorded the activity of the visual system in each
kitten by inserting a tungsten electrode into the sedated kitten’s
visual cortex of the brain, which let them monitor the activity of each
cortical cell separately. The tungsten rod detected electrical activity
or inactivity in the cortex, which indicated whether or not the visual
cortex retrieved information from the previously sutured eye. By
recording electrical activity in the kittens’ visual cortex, Hubel and
Wiesel observed how the cells of the visual cortex reacted to different
stimuli from both eyes and whether or not there was a difference in the
signals from the previously sutured eye and the normal eye.

Next,
Wiesel and Hubel showed the kittens different patterns of light to
stimulate the cortical cells. Normally, about eighty-five percent of
cortical cells respond identically to both eyes in a mammal with normal
vision and only fifteen percent of those cells respond to one eye only.
However, when Hubel and Wiesel performed the experiment on kittens with
previously sutured eyes, they found that one out of eighty-four cells
responded to the previously sutured eye and the other eighty-three cells
responded to the normal eye only. That meant that the cortical cells
redistributed to favor the normal eye, as it was their only source of
visual information during the early development of the kitten. The
researchers also noted that all kittens who had one of their eyes
sutured had some cortical cells that did not respond to any stimuli at
all. The researchers concluded that those cells were likely only
associated with the previously sutured eye. Because those cells did not
respond at all to any visual stimuli, they had not regenerated and could
not be used again. That meant that some cortical neuron function can be
fully lost if a vision impairment occurs during visual system
development.

Hubel and Wiesel also performed a simple vision
test on the kittens. They put an opaque barrier on one eye of the kitten
and monitored the kitten’s movement. They later repeated the same
procedure for the other eye. The researchers noted that when the kittens
were allowed to see with the previously sutured eye, they were
uncoordinated and showed no signs of vision. However, the normal eye
functioned properly and the researchers noted no impairment. Those
findings meant that the previously sutured eye had lost its vision
function and was not able to recover upon being open, which provided
further evidence that previous vision deprivation affects long-term
vision. Hubel and Wiesel concluded that an abnormality occurred
somewhere within the visual pathway from the eye to the brain that
caused the cortical neurons to redistribute and function only with the
normal eye.

Hubel and Wiesel investigated where in the vision
pathway the abnormality of vision cells came from. They sought to know
whether the abnormality was a cortical or a geniculate abnormality, as
that information would reveal how the vision pathway works. Another
question that they asked was whether or not depriving the kittens of
light or form (sight of object) caused the abnormality in the vision
pathway. Their research aimed to explain how the deprivation of either
one related to the continuous vision impairment in children after
surgery. Hubel and Wiesel also questioned if the kittens’ visual system
reacted to the visual impairment the same way the system of an older or
an adult cat would. Their findings sought to explain whether the
connections made by the visual system before birth were innate or
developed after birth. Finally, Hubel and Wiesel questioned whether the
neural connections would deteriorate if an impairment was present, or
whether the neural connections could not develop in the presence of an
impairment. To answer those questions, Hubel and Wiesel performed
multiple experiments with kittens and adult cats.

Following
the vision tests, Hubel and Wiesel sought to answer where the
abnormality occurred and how it worked. They checked the lateral
geniculate body, which is a transfer site in the thalamus that receives
visual information from the retina and transfers it to the occipital
lobe of the brain. The cells in the lateral geniculate body normally
respond more to one eye than the other. The vast majority of the
geniculate cells that were associated with the previously sutured eye
were intact and worked properly. However, upon analyzing those cells
with a microscope, Hubel and Wiesel found that the cross sectional area
of the lateral geniculate body had shrunk an average of forty percent
and that some geniculate cells were smaller and contained little
substance inside. That meant that the cells were not being used nearly
as much as they could have been, causing the entire area to atrophy. The
lateral geniculate body atrophied because it was receiving only half of
its normal visual information, but it continued to transfer visual
information from the eye to the brain. The researchers found no other
physical abnormalities anywhere along the visual pathway. Hubel and
Wiesel concluded that the abnormality that caused vision loss of the
sutured eye likely occurred somewhere in the cortex of the brain, which
was the last stop in the visual pathway.

Next, Hubel and
Wiesel investigated whether the visual impairment in the kittens was
caused by the deprivation of light or the depreciation of viewing forms.
Light refers to colors as well as light or dark perception of the eye,
while form refers to recognizing shapes of different objects. To
determine the cause of the visual impairment, the researchers took the
newborn kittens and put an opaque barrier over one of their eyes, which
reduced the incoming amount of light to only ten to one hundred times.
However, the barrier did not allow the kittens to distinguish forms or
shapes. The results indicated that cortical cells only responded to the
open eye, but the morphological changes in the lateral geniculate body
cells were significantly reduced. Those findings suggested that cortical
cells redistributed due to form deprivation, while the morphological
abnormalities of the lateral geniculate body were due to light
deprivation.

Next, Hubel and Wiesel investigated whether
those visual effects would be replicated in older kittens that had
already experienced vision. For that purpose, they sutured the eye of
kittens shut at nine weeks of age for one month. Upon opening the eye,
the researchers found that the distribution of cortical cells between
eyes was still largely in favor of the open eye. However, there was
almost no difference to the lateral geniculate body size. That, once
again, established that the source of abnormality was cortical and not
geniculate.

The researchers also tried the experiment with adult
cats. They observed after visually depriving adult cats for several
months, that the cats did not display any changes in cortical cell
distribution or changes in the morphology of their lateral geniculate
bodies. Hubel and Wiesel concluded that younger kittens were most at
risk for developing cortical abnormalities and, thus, blindness. That
risk declined with every month of life and was almost non-existent in
adults. Hubel and Wiesel found that there was a period at the beginning
of kitten’s life when the ability to view light and forms was most
important for development.

Finally, Hubel and Wiesel
researched whether visual pathway connections were present at birth and
deteriorated with disuse or whether they did not develop if not used
early on. To determine that, they experimented with three more kittens.
The researchers closed the eye of one of the kittens when the kitten was
eight days old, which is about the time that eyes first start to open in
kittens. They closed the eyes of the other two kittens after one to two
weeks of age. The researchers studied the electrical connections in the
brain at birth for all three kittens and found that their cortical cells
responded to visual stimuli similarly to those in adult cats. This
observation meant that the cortical cells had some ocular dominance.
However, the cats could recognize the stimuli from both eyes. Hubel and
Wiesel studied the same electrical connections in the brain later, after
reopening the sutured eyes, and found that they had deteriorated and
that cortical cells had redistributed in favor of the normal eye yet
again. Hubel and Wiesel concluded that the neural pathways in the visual
system are present at birth and deteriorate with disuse.

Hubel and Wiesel’s experiment helped uncover how the visual
system develops in mammals. First, they found a critical period during
which the visual system developed and learned that the deprivation of
vision during that time could impair vision forever. The conclusions of
Hubel and Wiesel’s experiment led surgeons to operate on congenital
cataracts as soon as the infant was diagnosed. In 1981, Hubel and Wiesel
received a Nobel Prize for Physiology or Medicine for their research on
the development of the visual system.